Non-invasive imaging of small animals, particularly molecular imaging (SPECT and PET) using radioactive tracers, has emerged as a valuable tool in biomedical research. Because of the specialized hardware required, the growth of micro-SPECT and micro-PET imaging has been limited mainly to dedicated research facilities with the funds and space to accommodate these devices. At clinical facilities, such resources are less available. However, SPECT cameras are widely employed for clinical imaging and could be used after hours by researchers for small animal imaging. Of particular interest are pinhole micro-SPECT imagers using clinical gamma camera detectors. Prior research on pinhole micro-SPECT has shown that the high magnification factor from pinhole collimation allows 1-2 mm spatial resolution to be attained. Previously published work on pinhole micro-SPECT has involved surplus gamma cameras dedicated for research use, with specialized attached hardware and separate calibration procedures. However, these characteristics prevent such designs from being practical for use in a clinical environment. In the proposed work, an innovative micro-SPECT imager with several key features will be developed to overcome these limitations. Our micro-SPECT will be truly portable. The design uses integrated pinhole apertures and does not require specialized mounting hardware, since it is placed directly on the patient imaging table. Our micro-SPECT will also be auto-calibrating. The mechanical alignment is computed directly from the scan data, and the alignment parameters are incorporated into the 3D reconstruction algorithm. In our proposed project, we will develop, optimize, and characterize the performance of a micro-SPECT imager based on this design. Because of these unique features (truly portable and auto-calibrating), our device will enable practical micro-SPECT imaging on conventional clinical gamma cameras, either after hours or during breaks in the clinical schedule. Furthermore, it would be possible for institutions to own multiple micro-SPECT imagers of our design, since the resources required for scale-up are minimal. As a result of this work, several other planned pre-clinical research projects at our institution will benefit directly from the availability of micro-SPECT imaging. Our work may also lead to a commercial product for ultra-low cost micro-SPECT imaging that would benefit many other researchers.